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Review
. 2020 Dec 15;85(5):635-642.
doi: 10.1097/QAI.0000000000002496.

Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development

Elizabeth Anne Martin  1 , Ming-Tain Lai  2 , Winnie Ngo  2 , Meizhen Feng  2 , Donald Graham  2 , Daria J Hazuda  2 , Sushma Kumar  3 , Carey Hwang  1 , Peter Sklar  1 , Ernest Asante-Appiah  2
Affiliations
Review

Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development

Elizabeth Anne Martin et al. J Acquir Immune Defic Syndr. .

Abstract

Background: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) approved for the treatment of HIV-1 infection in patients with no known DOR resistance-associated mutations. DOR was rationally designed to address limitations associated with other approved NNRTIs, particularly resistance from common NNRTI resistance-associated mutants containing K103N, Y181C, or G190A reverse transcriptase substitutions.

Setting: Data to date from both in vitro studies and clinical trials have been compiled to summarize the resistance profile of DOR.

Methods: We analyzed data from in vitro studies and phase 2 and 3 trials to assess the emergence of resistance-associated mutations and their impact on efficacy among participants treated with DOR.

Results: DOR exhibited a distinct resistance profile compared with efavirenz and rilpivirine in vitro and in vivo; mutant viruses that were resistant to DOR showed limited cross-resistance to efavirenz and rilpivirine. In clinical trials, the development of DOR resistance-associated substitutions in reverse transcriptase was uncommon.

Conclusion: Overall, minimal cross-resistance across NNRTIs was observed for DOR and limited development of DOR-related resistance. These data should assist clinicians in further understanding the resistance profile of DOR, so appropriate treatment decisions can be made for their patients.

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Conflict of interest statement

All authors are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, and may hold stock in Merck & Co., Inc., Kenilworth, NJ.

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